A transcriptomic approach for studying the activation of dendritic cells in response to mycobacterial infections

Mycobacterium tuberculosis (M. tuberculosis) is responsible for 2 million deaths annually. In recent years co-infection with HIV and drug-resistant strains has led to the increase in clinical cases of tuberculosis. BCG is the only vaccine currently available but is ineffective against adult pulmonary forms of the disease. Understanding the principle components of the host immune response against the pathogen will aid in the design of a better vaccine. Dendritic cells are potent antigen presenting cells that play a key role in priming naïve T cells. Effective T cell priming is necessary for a successful protective immune response in the host against the pathogen. I have been investigating the interaction of dendritic cells with M. tuberculosis, with a view to better understanding the signalling pathways affecting priming of anti-mycobacterial T cells by dendritic cells. Using DNA microarray and bio-informatics, I have been able to study early transcriptional signatures of bone marrow-derived dendritic cells (BMDCs) in response to M. tuberculois infection. Interferon Regulatory Factors (IRFs) and NFkB (Nuclear Factor kappa B) appear to be the principal transcription factors involved in regulating the cellular responses in M. tuberculosis infected BMDCs. It has been found that IRFs can function independent of the adaptor MyD88 (Myeloid Differentiation Factor 88) in M. tuberculosis infected BMDCs, which is surprising considering the important role played by MyD88 in the Toll mediated signalling pathway. Exvivo experiments also show that MyD88 may not be absolutely essential for mounting anti-mycobacterial T cell responses. Hence immune responses generated by M. tuberculosis infected BMDCs appear to be mediated via the MyD88 dependent and independent pathways.

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of London

Year dc:date.issued

2007

Author dc:creator

• Krishnan, Nitya

• Department of Infection

Language dc:language

en, eng